The neurocognitive process of preference-based decisions

This thesis focused on three aspects of human preference-based decisions. First, integrating multiple sources of value information had an impact on behavioural performance and the underlying cognitive process. During preference-based judgments, humans combine multiple information sources into a single source of evidence, and behavioural changes are related to the quality of evidence. Second, to investigate psychophysical performance (sensitivity and bias) based on internal value and external perception information, a categorization task was conducted with value information embedded into geometric shapes. As measured by Weber ratio, attaching internal values to geometric shapes resulted in less discriminating sensitivity than perceptual judgements, and there was no difference in the response bias between the two types of decisions. Hence, these findings showed that a single computational process may underlie both value-based and perceptual decisions, and that transferring internal preference onto external perceptual input generates additional noise to the decision-making process. Third, this thesis investigated the MEG signatures of internal value-based decisions as well as their differences from perceptual decisions. Instead of geometrical shapes, internal value information embedded into spatial locations and binary choice task was conducted using the identical visual stimuli in both the internal preference and external perception context. Multivariate patten analysis on source space MEG data showed that more extended visual and frontoparietal activations are sensitive to value differences in value-based decisions. These results provide a foundation for further integrating perceptual and preference-based decisionmaking into a single framework. Overall, findings presented in this thesis contributes to the study of value-based decision-making by integrating novel experimental approaches, cognitive modelling, and electrophysiological investigations of the human brain

Prevalence of intestinal parasitosis and immunological status of HIV/AIDS patients on antiretroviral therapy in Nyanya General Hospital Abuja, Nigeria

Intestinal parasites, especially in HIV/AIDS patients, are a leading cause of morbidity and mortality worldwide. The aim of this study was to determine the prevalence of intestinal parasitosis and the immune status of HIV/AIDS patients on ART. Two hundred (200) HIV/AIDS patients were recruited from the ART clinic at Nyanya General Hospital in Abuja, Nigeria, for this cross-sectional institution-based research. To collect detailed demographic data, questionnaires were sent out. The direct wet mount, formol-ether concentration, and adjusted Ziehl-Neelsen staining were used to analyze stool samples. Patients' records were analyzed during this study period to assess their CD4+ T-cell count and viral load status. The findings were compared using a contingency table analysis and the chi-square test. The Mann-Whitney test was used to compare quantitative data sets. P value of 0.05 was described as statistically significant (P≤0.05).The findings of our study were 80 (40 percent) of the patients had intestinal parasitosis, with 11 (13.8 percent) of them having multiple parasitosis. Cryptosporidium parvum had the highest prevalence (16%), Entamoeba histolytica /dispar (13%), Giardia lamblia (7%), and Entamoeba coli (3.5%). Strongyloides stercoralis, Ascaris lumbricoides, and Cystoisospora belli each had a prevalence of 2.5 percent. The findings revealed that diarrhoea was linked to cryptosporidiosis, giardiasis, and cystoisosporiasis. In this study, there was no correlation between intestinal parasitosis and immune system function. In HIV/AIDS patients, prolonged and untreated diarrhoea can be crippling and fatal

Rapid prediction of crucial hotspot interactions for icosahedral viral capsid self-assembly by energy landscape atlasing validated by mutagenesis

Icosahedral viruses have their infectious genome encapsulated by a shell assembled by a multiscale process, starting from an integer multiple of 60 viral capsid or coat protein (VP) monomers. We predict and validate inter-atomic hotspot interactions between VP monomers that are important for the assembly of 3 icosahedral viral capsids: Adeno Associated Virus serotype 2 (AAV2) and Minute Virus of Mice (MVM), both T=1 single stranded DNA viruses, and Bromo Mosaic Virus (BMV), a T=3 single stranded RNA virus. Experimental validation is by in-vitro, site-directed mutagenesis data found in literature. We combine ab-initio predictions at two scales: at the interface-scale, we predict the importance (cruciality) of an interaction for successful subassembly across each interface between VP monomers; and at the capsid-scale, we predict the cruciality of an interface for successful capsid assembly. At the interface-scale, we measure cruciality by changes in the capsid free-energy landscape partition function when an interaction is removed. The partition function computation uses atlases of interface subassembly landscapes, rapidly generated by a novel geometric method and curated opensource software EASAL (efficient atlasing and search of assembly landscapes). At the capsid-scale, cruciality of an interface for successful assembly of the capsid is based on combinatorial entropy. Our study goes from resource-light, multiscale computational predictions of crucial hotspot inter-atomic interactions to validation using data on site-directed mutagenesis' effect on capsid assembly. By reliably and rapidly narrowing down target interactions, (no more than 1.5 hours per interface on a laptop with Intel Core i5-2500K 3.2Ghz CPU and 8GB of RAM) our predictions can inform and reduce time-consuming in-vitro and in-vivo experiments, or more computationally intensive in-silico analyses

A systematic evaluation of source reconstruction of resting MEG of the human brain with a new high-resolution atlas: performance, precision, and parcellation

Noninvasive functional neuroimaging of the human brain can give crucial insight into the mechanisms that underpin healthy cognition and neurological disorders. Magnetoencephalography (MEG) measures extracranial magnetic fields originating from neuronal activity with high temporal resolution, but requires source reconstruction to make neuroanatomical inferences from these signals. Many source reconstruction algorithms are available, and have been widely evaluated in the context of localizing task-evoked activities. However, no consensus yet exists on the optimum algorithm for resting-state data. Here, we evaluated the performance of six commonly-used source reconstruction algorithms based on minimum-norm and beamforming estimates. Using human resting-state MEG, we compared the algorithms using quantitative metrics, including resolution properties of inverse solutions and explained variance in sensor-level data. Next, we proposed a data-driven approach to reduce the atlas from the Human Connectome Project's multi-modal parcellation of the human cortex based on metrics such as MEG signal-to-noise-ratio and resting-state functional connectivity gradients. This procedure produced a reduced cortical atlas with 230 regions, optimized to match the spatial resolution and the rank of MEG data from the current generation of MEG scanners. Our results show that there is no “one size fits all” algorithm, and make recommendations on the appropriate algorithms depending on the data and aimed analyses. Our comprehensive comparisons and recommendations can serve as a guide for choosing appropriate methodologies in future studies of resting-state MEG

Economic benefits and costs of surgery for filarial hydrocele in Malawi

Background Lymphatic filariasis (LF) is endemic in 72 countries of Africa, Asia, Oceania, and the Americas. An estimated 25 million men live with the disabling effects of filarial hydrocele. Hydrocele can be corrected with surgery with few complications. For most men, hydrocelectomy reduces or corrects filarial hydrocele and permits them to resume regular activities of daily living and gainful employment. Methodology and principal findings This study measures the economic loss due to filarial hydrocele and the benefits of hydrocelectomy and is based on pre- and post-operative surveys of patients in southern Malawi. We find the average number of days of work lost due to filarial hydrocele and daily earnings for men in rural Malawi. We calculate average annual lost earnings and find the present discounted value for all years from the time of surgery to the end of working life. We estimate the total costs of surgery. We compare the benefit of the work capacity restored to the costs of surgery to determine the benefit-cost ratio. For men younger than 65 years old, the average annual earnings loss attributed to hydrocele is US$126. The average discounted present value of lifetime earnings loss for those men is US$1684. The average budgetary cost of the hydrocelectomy is US$68. The ratio of the benefit of surgery to its costs is US$1684/US$68 or 24.8. Sensitivity analysis demonstrates that the results are robust to variations in cost of surgery and length of working life. Conclusion The lifetime benefits of hydrocelectomy–to the man, his family, and his community–far exceed the costs of repairing the hydrocele. Scaling up subsidies to hydrocelectomy campaigns should be a priority for governments and international aid organizations to prevent and alleviate disability and lost earnings that aggravate poverty among the many millions of men with filarial hydrocele

Metagenomic profiling of ticks: Identification of novel rickettsial genomes and detection of tick-borne canine parvovirus

Background: Across the world, ticks act as vectors of human and animal pathogens. Ticks rely on bacterial endosymbionts, which often share close and complex evolutionary links with tick-borne pathogens. As the prevalence, diversity and virulence potential of tick-borne agents remain poorly understood, there is a pressing need for microbial surveillance of ticks as potential disease vectors. Methodology/Principal Findings: We developed a two-stage protocol that includes 16S-amplicon screening of pooled samples of hard ticks collected from dogs, sheep and camels in Palestine, followed by shotgun metagenomics on individual ticks to detect and characterise tick-borne pathogens and endosymbionts. Two ticks isolated from sheep yielded an abundance of reads from the genus Rickettsia, which were assembled into draft genomes. One of the resulting genomes was highly similar to Rickettsia massiliae strain MTU5. Analysis of signature genes showed that the other represents the first genome sequence of the potential pathogen Candidatus Rickettsia barbariae. Ticks from a dog and a sheep yielded draft genome sequences of Coxiella strains. A sheep tick yielded sequences from the sheep pathogen Anaplasma ovis, while Hyalomma ticks from camels yielded sequences belonging to Francisella-like endosymbionts. From the metagenome of a dog tick from Jericho, we generated a genome sequence of a canine parvovirus. Significance: Here, we have shown how a cost-effective two-stage protocol can be used to detect and characterise tick-borne pathogens and endosymbionts. In recovering genome sequences from an unexpected pathogen (canine parvovirus) and a previously unsequenced pathogen (Candidatus Rickettsia barbariae), we demonstrate the open-ended nature of metagenomics. We also provide evidence that ticks can carry canine parvovirus, raising the possibility that ticks might contribute to the spread of this troublesome virus

The interindividual variability of multimodal brain connectivity maintains spatial heterogeneity and relates to tissue microstructure

Humans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV